HO-1 controls heme regulatory pool in erythroid cells. (A) When overexpressed, HO-1 causes depletion of heme in the heme regulatory pool. This leads to a secondary decrease in TfR expression and iron uptake by the cell. Moreover, reduction in heme levels results in increased HRI activity that, in turn, represses globin translation. (B) On the other hand, when HO-1 is absent, an expansion of the heme regulatory pool results in a mainly transcriptional activation of TfR expression and an enhanced iron uptake by the cell. The increase in the heme levels also represses HRI activity, leading to augmented globin translation. Under physiological conditions, appropriate levels of HO-1 guarantee optimal hemoglobinization rates.